DESCRIPTION: The long range goal is to develop new strategies for the treatment of HIV-disease based on intra-cellular immunization delivered via retrovirus vectors. However, current murine retrovirus-based systems have for the most part failed to transduce primary human cells with the efficiency needed to successfully cure a genetic or infectious disease. In addition they are limited by their inability to infect non-dividing cells. This has been a significant hindrance for the transduction of human hematopoietic stem/early progenitor cells. Lentiviruses such as HIV are able to infect some non-dividing terminally differentiated cells. In addition HIV efficiently infects primary human CD4+ cells. In this application, the investigator proposes to harness the ability of HIV to infect primary human cells and establish a packaging system for gene transfer and gene therapy (Specific Aim 1). In order to expand the tropism of this producer line beyond that of HIV, he will incorporate heterologous envelope genes which have been shown to infect a variety of tissues and species. In addition, he will develop retrovirus vectors to be used with the HIV-based producer line (Specific Aim 2). This strategy at a minimum will complement and expand the currently available murine-based retroviral gene transfer systems and optimally has the potential to facilitate the implementation of human gene therapy protocols for the treatment of HIV disease.